Lung homing T-cell generation is dependent on strength and timing of antigen delivery to lymph nodes

Inhaled allergens are known for their immediate and ongoing effects in the respiratory tract (RT). In this report, we track inhaled antigen in normal mice for 7 days and find that while it is cleared from the airways, inhaled antigen persists in peripheral lung tissue and the draining lymph nodes (DLNs). The persistence of antigen led to ongoing presentation in the lymph nodes, but not the lungs, that decreased with time in direct proportion with the frequency of antigen-bearing RT dendritic cells (DCs). There was evidence of functional changes among the antigen-bearing DCs in the lymph nodes, as the expression of CD40, CD80 and CD86 were modulated over the course of 7 days. At the same time, there was a decrease in both CD4(+) T-cell proliferation in lymph nodes and the generation of recirculating CD4(+) T cells. However, early presentation of lower doses of inhaled antigen also resulted in a decrease in CD4(+) T-cell proliferation and recirculation. Thus, T-cell recirculation depends on the strength of stimulus in the DLNs and is produced by a combination of the dose of antigen delivered to the RT, DC migration and co-stimulatory molecule expression. These results provide an important insight into the fate of inhaled antigen in vivo and the influence of persistent antigen presentation on T-cell activation in the lymph nodes.